The essential plan of this proposal is to use oocyte microinjection to create strains of mice that are tolerant to the species specific determinants that distinguish human class I, DR, DC, or SB antigens as a group from their murine analogues independent of their allelic viriations. These strains of mice should thus provide superior animals for recognizing allele specific determinants in the human MHC and for generating antibodies capable of recognizing those determinants. In addition, monoclonal antibodies produced in this project should be capable of subdividing known HLA antigens and should prove useful in identifying more specicfic MHC markers of disease susceptibility. These antibodies will then be applied, in parallel with gene sequencing studies, to generate precise reagents for distinguishing alleles and haplotypes most prone to various MHC associated disease.